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Carbonic anhydrases are ubiquitous enzymes that catalyze the reverse hydration and dehydration of carbon dioxide and bicarbonate respectively. A variety of tumors in humans show overexpression of human carbonic anhydrase II (HCA II) leading to an acidic breakdown of carbon dioxide into bicarbonate. While a variety of drug inhibitors exist, many come with undesirable side effects. Using non-conical amino acids (ncAAs), we probe an adjacent residue (Phe 93) to one of three key histidine residues involved in the active site. This shifting of a histidine residue creates a non-optimal proton transfer and thus, decreasing catalytic efficiency. The goal of this study was to better understand the catalytic flexibility and efficiency of HCA II without compromising protein stability. What we found was unexpected: exchanging phenylalanine with p-bromophenylalanine (pBrF) has a slight decrease in enzymatic activity while the exchange with p-nitrophenylalanine (pNO2F) significantly increased enzymatic activity in both an optimal pH of 7.4 and a more acidic pH of 6.4 compared to WT HCA II. In addition, stability of pNO2F mutant protein is significantly increased in pH conditions ranging from 7.4 to 9.4 compared to wild-type HCA II. Finally, the stability of pBrF mutant is comparable or even slightly higher than wild-type HCA II in pH conditions ranging from 7.4 to 9.4. This data suggests that Phe 93 plays a role in influencing the coordination of His 94, one of three key residues that coordinate a zinc ion involved in protein transfer; additionally, further studies of this residue may lead to potential cancer treatments based on the pBrF mutant and industrial applications based on the pNO2F mutant.